PROJECT SUMMARY & ABSTRACT Carotid atherosclerosis is a contributing cause of stroke, the second leading cause of death worldwide. Various features of plaque morphology, such as plaque structure and composition, may allow improved risk assessment of carotid plaque rupture and stroke. Quantitative ultrasound (QUS) methods for evaluation of plaque echogenicity have been used to determine plaque morphology. For example, ?low? grayscale median (GSM) values have been associated with plaques having worrisome features that may indicate propensity to rupture, such as large lipid cores. While this technique is promising, the range of ?low? GSM values reported in the literature is large, suggesting that the ultrasound system and settings used for image acquisition and analysis may influence the GSM value, making widespread clinical implementation of the GSM value difficult. Thus, the primary goal of the proposed research is to develop an accurate, noninvasive tool for QUS assessment of carotid plaque composition that may be less dependent upon instrumentation. Our preliminary studies show that estimation of integrated backscatter (IB) and attenuation coefficient (AC) QUS parameters may correlate with histopathology assessments and may objectively assess carotid plaque composition. However, IB estimations often do not incorporate a necessary correction for signal loss between the transducer and plaque. We have completed preliminary studies showing the feasibility of IB and AC estimation and demonstrated that our approach has merit. For the first portion of this proposed investigation, ultrasound data that have already been collected as part of an ongoing study on carotid plaque structure will be used. We plan to optimize our signal processing algorithms and improve the spatial resolution of our QUS images to improve in-vivo classification of carotid plaque tissue. The second portion of this proposed investigation will validate and test the correspondence of in-vivo and ex-vivo QUS parameters with 3D reconstructed histopathology sections. We will collect high-frequency ultrasound data and perform serial histopathology sectioning on plaques after excision. Our QUS parameters will be calculated in excised plaques and compared with in-vivo QUS parameter results and 3D reconstructed histopathology sections that identify regions of lumen, calcified, lipidic, and fibrous tissue. This proposal lays the foundation for evaluating IB and AC to accurately characterize heterogeneous carotid plaque by its composition. In addition, these QUS parameters will guide future development of an accurate and reliable clinical tool for assessing the risk of plaque rupture or stroke by plaque echogenicity changes. Training will be completed at the University of Wisconsin-Madison. A multidisciplinary team has been assembled in support of this project. Training will include regular meetings with clinicians and other personnel to strengthen the quality and clinical utility of this work.